Investigations are planned which are directed at the delineation of the mechanisms by which insulin and glucagon effect the short-term and long-term regulation of the activities of acetyl-CoA carboxylase, fatty acid synthetase and beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase in mammalian liver. These studies will be carried out with isolated cells, tissue cultures and whole animals. Studies on acetyl-CoA carboxylase will concentrate initially on the mechanism by which glucagon decreases fatty acid synthesis in 1-hour incubations with isolated hepatocytes. Studies will also be carried out on the purification and identity of a rat liver cytosolic factor that inactivates acetyl-CoA carboxylase activity. Investigations on the fatty acid synthetase complex will concentrate on the mechanism by which insulin regulates the rate of synthesis of mRNA for this protein. Studies on HMG-CoA reductase will concentrate on determinations of the activities of HMG-CoA reductase activating and inactivating enzymes in livers of animals subjected to different nutritional and hormonal states. We will also continue our attempts to purify these enzyme systems to homogeneity.